Mouse central nervous system contains a family of polypeptides that are structurally related to myelin basic protein (MBP). A variety of genetic determinants and epigenetic factors have been identified that regulate the expression of MBP-related gene products in the mouse brain. In this application we propose to analyze the structures of the different MBP-related gene products by cloning and sequencing MBP-specific cDNA from mouse brain. We will use restriction fragment length polymorphisms associated with MBP-specific sequences in inbred and recombinant inbred mouse genomic DNA to determine the chromosomal locations of MBP structural gene(s) and MBP regulator genes. We will use MBP-specific cDNA probes to study MBP gene expression in wild type and mutant mouse brain and in primary cultures of mouse and rat brain. The results will: delineate and characterize the genetic and epigenetic factors that regulate MBP gene expression in the brain, reveal the molecular mechanisms responsible for the structural polymorphism of MBP-related gene products and for regulating their expression, and elucidate the functional relationship between MBP gene expression and myelin morphogenesis. This will further our understanding of the pathogenesis of a variety of birth defects and degenerative diseases that affect myelin in humans.